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Am J Physiol Cell Physiol 277: C777-C790, 1999;
0363-6143/99 $5.00
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Vol. 277, Issue 4, C777-C790, October 1999

Effects of macromolecular transport and stochastic fluctuations on dynamics of genetic regulatory systems

Paul Smolen, Douglas A. Baxter, and John H. Byrne

Department of Neurobiology and Anatomy, W. M. Keck Center for the Neurobiology of Learning and Memory, The University of Texas-Houston Medical School, Houston, Texas 77225

To predict the dynamics of genetic regulation, it may be necessary to consider macromolecular transport and stochastic fluctuations in macromolecule numbers. Transport can be diffusive or active, and in some cases a time delay might suffice to model active transport. We characterize major differences in the dynamics of model genetic systems when diffusive transport of mRNA and protein was compared with transport modeled as a time delay. Delays allow for history-dependent, non-Markovian responses to stimuli (i.e., "molecular memory"). Diffusion suppresses oscillations, whereas delays tend to create oscillations. When simulating essential elements of circadian oscillators, we found the delay between transcription and translation necessary for oscillations. Stochastic fluctuations tend to destabilize and thereby mask steady states with few molecules. This computational approach, combined with experiments, should provide a fruitful conceptual framework for investigating the function and dynamic properties of genetic regulatory systems.

transcriptional regulation; transport delays; circadian oscillations; multistability; genetic modeling


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